tRNA Binds to Cytochrome c and Inhibits Caspase Activation

Yide Mei; Jeongsik Yong; Hongtu Liu; Yigong Shi; Judy Meinkoth; Gideon Dreyfuss; Xiaolu Yang

doi:10.1016/j.molcel.2010.01.023

tRNA Binds to Cytochrome c and Inhibits Caspase Activation

Yide Mei
, Jeongsik Yong
, Hongtu Liu
, Yigong Shi
, Judy Meinkoth
, Gideon Dreyfuss
, Xiaolu Yang

Biochemistry, Molecular Biology, and Biophysics (CBS)

Research output: Contribution to journal › Article › peer-review

180 Scopus citations

Abstract

The specific molecular events that characterize the intrinsic apoptosis pathway have been the subject of intense research due to the pathway's fundamental role in development, homeostasis, and cancer. This pathway is defined by the release of cytochrome c from mitochondria into the cytosol and subsequent binding of cytochrome c to the caspase activator Apaf-1. Here, we report that both mitochondrial and cytosolic transfer RNA (tRNA) bind to cytochrome c. This binding prevents cytochrome c interaction with Apaf-1, blocking Apaf-1 oligomerization and caspase activation. tRNA hydrolysis in living cells and cell lysates enhances apoptosis and caspase activation, whereas microinjection of tRNA into living cells blocks apoptosis. These findings suggest that tRNA, in addition to its well-established role in gene expression, may determine cellular responsiveness to apoptotic stimuli.

Original language	English (US)
Pages (from-to)	668-678
Number of pages	11
Journal	Molecular Cell
Volume	37
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2010.01.023
State	Published - Mar 12 2010

Bibliographical note

Funding Information:
We thank Drs. K. Shogen and W. Ardelt for providing onconase, Dr. X. Wang for providing Apaf-1 −/− and wild type MEFs and anti-Apaf-1 antibody, Dr. K. Dittmar for advice on tRNA work, and A. Stonestrom and S. Slattery for help with manuscript preparation. This work was supported, in part, by NIH grants GM060911 and CA108872 and a Leukemia and Lymphoma Society Scholar Award (to X.Y.). G.D. is funded by the Howard Hughes Medical Institute.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

HUMDISEASE
PROTEINS
RNA

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10.1016/j.molcel.2010.01.023

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title = "tRNA Binds to Cytochrome c and Inhibits Caspase Activation",

abstract = "The specific molecular events that characterize the intrinsic apoptosis pathway have been the subject of intense research due to the pathway's fundamental role in development, homeostasis, and cancer. This pathway is defined by the release of cytochrome c from mitochondria into the cytosol and subsequent binding of cytochrome c to the caspase activator Apaf-1. Here, we report that both mitochondrial and cytosolic transfer RNA (tRNA) bind to cytochrome c. This binding prevents cytochrome c interaction with Apaf-1, blocking Apaf-1 oligomerization and caspase activation. tRNA hydrolysis in living cells and cell lysates enhances apoptosis and caspase activation, whereas microinjection of tRNA into living cells blocks apoptosis. These findings suggest that tRNA, in addition to its well-established role in gene expression, may determine cellular responsiveness to apoptotic stimuli.",

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author = "Yide Mei and Jeongsik Yong and Hongtu Liu and Yigong Shi and Judy Meinkoth and Gideon Dreyfuss and Xiaolu Yang",

note = "Funding Information: We thank Drs. K. Shogen and W. Ardelt for providing onconase, Dr. X. Wang for providing Apaf-1 −/− and wild type MEFs and anti-Apaf-1 antibody, Dr. K. Dittmar for advice on tRNA work, and A. Stonestrom and S. Slattery for help with manuscript preparation. This work was supported, in part, by NIH grants GM060911 and CA108872 and a Leukemia and Lymphoma Society Scholar Award (to X.Y.). G.D. is funded by the Howard Hughes Medical Institute. ",

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doi = "10.1016/j.molcel.2010.01.023",

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AU - Mei, Yide

AU - Yong, Jeongsik

AU - Liu, Hongtu

AU - Shi, Yigong

AU - Meinkoth, Judy

AU - Dreyfuss, Gideon

AU - Yang, Xiaolu

N1 - Funding Information: We thank Drs. K. Shogen and W. Ardelt for providing onconase, Dr. X. Wang for providing Apaf-1 −/− and wild type MEFs and anti-Apaf-1 antibody, Dr. K. Dittmar for advice on tRNA work, and A. Stonestrom and S. Slattery for help with manuscript preparation. This work was supported, in part, by NIH grants GM060911 and CA108872 and a Leukemia and Lymphoma Society Scholar Award (to X.Y.). G.D. is funded by the Howard Hughes Medical Institute.

PY - 2010/3/12

Y1 - 2010/3/12

N2 - The specific molecular events that characterize the intrinsic apoptosis pathway have been the subject of intense research due to the pathway's fundamental role in development, homeostasis, and cancer. This pathway is defined by the release of cytochrome c from mitochondria into the cytosol and subsequent binding of cytochrome c to the caspase activator Apaf-1. Here, we report that both mitochondrial and cytosolic transfer RNA (tRNA) bind to cytochrome c. This binding prevents cytochrome c interaction with Apaf-1, blocking Apaf-1 oligomerization and caspase activation. tRNA hydrolysis in living cells and cell lysates enhances apoptosis and caspase activation, whereas microinjection of tRNA into living cells blocks apoptosis. These findings suggest that tRNA, in addition to its well-established role in gene expression, may determine cellular responsiveness to apoptotic stimuli.

AB - The specific molecular events that characterize the intrinsic apoptosis pathway have been the subject of intense research due to the pathway's fundamental role in development, homeostasis, and cancer. This pathway is defined by the release of cytochrome c from mitochondria into the cytosol and subsequent binding of cytochrome c to the caspase activator Apaf-1. Here, we report that both mitochondrial and cytosolic transfer RNA (tRNA) bind to cytochrome c. This binding prevents cytochrome c interaction with Apaf-1, blocking Apaf-1 oligomerization and caspase activation. tRNA hydrolysis in living cells and cell lysates enhances apoptosis and caspase activation, whereas microinjection of tRNA into living cells blocks apoptosis. These findings suggest that tRNA, in addition to its well-established role in gene expression, may determine cellular responsiveness to apoptotic stimuli.

KW - HUMDISEASE

KW - PROTEINS

KW - RNA

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DO - 10.1016/j.molcel.2010.01.023

M3 - Article

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AN - SCOPUS:77649264369

SN - 1097-2765

VL - 37

SP - 668

EP - 678

JO - Molecular Cell

JF - Molecular Cell

IS - 5

ER -

tRNA Binds to Cytochrome c and Inhibits Caspase Activation

Abstract

Bibliographical note

UN SDGs

Keywords

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